Advancements in nanotechnology for PARP inhibitor delivery: a comprehensive review of diverse nanosystems, their mechanisms, and therapeutic applications across cancer and beyond.

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors have appeared as a transformative class of anticancer agents, particularly for tumors with homologous recombination deficiencies such as BRCA1/2-mutated breast, ovarian, prostate, and pancreatic cancers. Despite their clinical success, challenges such as poor bioavailability, systemic toxicity, and acquired resistance have limited their broader application. Nanotechnology-based drug delivery systems offer a promising strategy to overcome these limitations by enhancing the solubility, stability, and tumor-specific accumulation of PARP inhibitors while reducing off-target effects. This review explores the mechanism of action of PARP inhibitors, including their role in DNA repair and synthetic lethality, and discusses their therapeutic applications. Furthermore, recent progresses in delivery systems, including lipid-based, polymeric, inorganic, and hybrid nanosystems, are examined with a focus on their design, functionality, and impact on drug efficacy. Recent studies demonstrating improved drug retention, enhanced tumor targeting, and controlled release mechanisms are highl'hted, along with potential strategies to overcome resistance. The integration of multifunctional and stimuli-responsive nanosystems further enhances the therapeutic potential of PARP inhibitors. Continued innovation in nanomedicine holds the potential to optimize PARP inhibitor therapy and expand its clinical utility in personalized cancer treatment. Future directions include addressing translational challenges, scalability, and regulatory considerations for clinical applications.